セロトニンアナログ^<18>F-メチルトリプトファンを用いたうつ病発症機序の基礎的研究

使用血清素类似物^<18>F-甲基色氨酸进行抑郁症发病机制的基础研究

• 批准号: 11670868
• 负责人: ENDO Keigo
• 金额: $ 2.11万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670868/
• 关键词: α-methyl tryptophan; ^<18>F-α-methyl tryptophan (^<18>FAMTP); Radiosynthesis; Serotonin metabolism; Tumor-detecting agent; F^<18>-αメチルタイロシン; パーキンソン病; 分裂病; うつ病; セロトニン; ^<18>Fα-メチルトリプトファン

F-18 alphamethyltryptophan (^<18>FAMTP) which is newly synthesized at our institute with use of Cyclotron system, is one of F-18 labeled amino acid reflecting the amino acid metabolism. The aim of this study was to synthesize the alpha-methyltryptophan with 18F positron nuclide and use this labeled molecule to investigate the potential utility of imaging diagnosis for neurotransmitter malfunction related with serotonin metabolism. Synthesis of ^<18>FAMTP was performed by direct electrophilic fluorination. In animal experiments, A volume of 100ul containing 370kBq of ^<18>FAMTP was injected into BALB/C female mice to measure bio-distribution at 10 minutes, 30 minutes and 60 minutes. By dissecting mice at each time, high uptakes were seen at heart, kidney and bone. Uptake at kidney at early time means rapid washout from kidney. High uptake in bone which is not like a ^<18>FAMT suggested that ^<18>FAMTP is unstable in vivo and resulted in high free ^<18>F ion. One characteristic is high uptake in heart. that suggest serotonic metabolism are taking place in heart muscle

F-18-N-甲基色氨酸（^<18>FAMTP）是我所利用回旋加速器合成的新产物，是反映氨基酸代谢的F-18标记氨基酸之一。本研究的目的是用18F正电子核素合成α-甲基色氨酸，并将其用于5-羟色胺代谢相关的神经递质功能障碍的影像学诊断。通过<18>直接亲电加成法进行了α-FAMTP的合成。在动物实验中，将含有370 kBq的100 μ l体积的1FAMTP<18>注射到BALB/C雌性小鼠中，以测量10分钟、30分钟和60分钟的生物分布。通过每次解剖小鼠，在心脏、肾脏和骨骼中观察到高摄取。肾脏早期摄取意味着从肾脏快速洗脱。在骨中的高摄取不像^<18>FAMT，这表明^<18>FAMTP在体内是不稳定的，并导致高游离^<18>F离子。一个特征是心脏中的高摄取。这表明心脏肌肉中发生了代谢紊乱

项目成果

Tomiyoshi Katsumi: "Metabolic Studies of 18-a-methyltyrosine in mice bering colorectal carcinoma LS-180"Anti-Cancer Drugs. 10. 329-336 (1999)

Tomiyoshi Katsumi：“结直肠癌 LS-180 小鼠中 18-α-甲基酪氨酸的代谢研究”抗癌药物。

Amano Shigeko: "In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer."J.Nucl.Med.. 39. 1424-1427 (1998)

Amano Shigeko：“PET 和 SPECT 放射性药物检测乳腺癌的体内比较。”J.Nucl.Med.. 39. 1424-1427 (1998)

Shigeko Amano.: "In vivo comparison of PET and SPECT radiopharmaceuticals in detecting breast cancer."J.Nucl.Med.. 39. 1424-1427 (1998)

Shigeko Amano.：“PET 和 SPECT 放射性药物检测乳腺癌的体内比较。”J.Nucl.Med.. 39. 1424-1427 (1998)

Katsumi Tomiyoshi: "Metabolic studies of [^<18>F-α-methyl]tyrosine in mice bearing colorectal carcinoma LS-180"Anti-Cancer Drugs. 10. 329-336 (1999)

Katsumi Tomiyoshi：“患有结肠直肠癌LS-180的小鼠中[^ 18 F-α-甲基]酪氨酸的代谢研究”抗癌药物。10. 329-336(1999)。

Tomio Inoue: "Accuracy of standardized uptake value measured by simultaneous emission and transmission scanning in PET oncology"Nuclear Meidicne Communications. 20. 849-857 (1999)

Tomio Inoue：“PET 肿瘤学中通过同步发射和传输扫描测量的标准化摄取值的准确性”Nuclear Medicne Communications。